Showing papers by "James P. Butler published in 1996"

Friction in airway smooth muscle: mechanism, latch, and implications in asthma

Abstract: Fredberg, J. J., K. A. Jones, M. Nathan, S. Raboudi, Y. S. Prakash, S. A. Shore, J. P. Butler, and G. C. Sieck. Friction in airway smooth muscle: mechanism, latch, and implications in asthma. J. Appl. Physiol. 81(6): 2703–2712, 1996.—In muscle, active force and stiffness reflect numbers of actin-myosin interactions and shortening velocity reflects their turnover rates, but the molecular basis of mechanical friction is somewhat less clear. To better characterize molecular mechanisms that govern mechanical friction, we measured the rate of mechanical energy dissipation and the rate of actomyosin ATP utilization simultaneously in activated canine airway smooth muscle subjected to small periodic stretches as occur in breathing. The amplitude of the frictional stress is proportional to ηE, where E is the tissue stiffness defined by the slope of the resulting force vs. displacement loop and η is the hysteresivity defined by the fatness of that loop. From contractile stimulus onset, the time course of frictional stress amplitude followed a biphasic pattern that tracked that of the rate of actomyosin ATP consumption. The time course of hysteresivity, however, followed a different biphasic pattern that tracked that of shortening velocity. Taken together with an analysis of mechanical energy storage and dissipation in the cross-bridge cycle, these results indicate, first, that like shortening velocity and the rate of actomyosin ATP utilization, mechanical friction in airway smooth muscle is also governed by the rate of cross-bridge cycling; second, that changes in cycling rate associated with conversion of rapidly cycling cross bridges to slowly cycling latch bridges can be assessed from changes of hysteresivity of the force vs. displacement loop; and third, that steady-state force maintenance (latch) is a low-friction contractile state. This last finding may account for the unique inability of asthmatic patients to reverse spontaneous airways obstruction with a deep inspiration.

Intracellular pressure is a motive force for cell motion in Amoeba proteus

Abstract: The cortical filament layer of free-living amoebae contains concentrated actomyosin, suggesting that it can contract and produce an internal hydrostatic pressure. We report here on direct and dynamic intracellular pressure (P(ic)) measurements in Amoeba proteus made using the servo-null technique. In resting apolar A. proteus, P(ic) increased while the cells remained immobile and at apparently constant volume. P(ic) then decreased approximately coincident with pseudopod formation. There was a positive correlation between P(ic) at the onset of movement and the rate of pseudopod formation. These results are the first direct evidence that hydrostatic pressure may be a motive force for cell motion. We postulate that contractile elements in the amoeba's cortical layer contract and increase P(ic) and that this P(ic) is utilized to overcome the viscous flow resistance of the intracellular contents during pseudopod formation.

Dihedral angles of septal “bend” structures in lung parenchyma

Abstract: Butler, J. P., E. H. Oldmixon, and F. G. Hoppin, Jr.Dihedral angles of septal “bend” structures in lung parenchyma. J. Appl. Physiol. 81: 1800–1806, 1996.—Alveolar parenchyma comprises two interact...

Contour of the gnrh pulse independently modulates gonadotropin secretion in the human male

Abstract: GnRH pulse frequency, amplitude, and interpulse interval have all been demonstrated to regulate gonadotropin secretion individually. We tested the hypothesis that the contour of the GnRH pulse also modulates gonadotropin output in 10 men with isolated GnRH deficiency in whom a fixed GnRH dose was administered at a constant physiologic frequency by either instantaneous bolus or by 1-, 5-, or 30-min infusions. LH, FSH and free alpha subunit (FAS) responses were also compared to spontaneous gonadotropin secretion in normal adult men. While the LH and FAS pulses following the instantaneous bolus and 1-min infusion of GnRH were indistinguishable, further increases in the duration of gonadotrope stimulation by GnRH were associated with progressive decreases in all parameters of gonadotropin secretion (mean levels, amplitude, peak levels, AUC). FSH secretion was also decreased following variations in the contour of the GnRH pulse, although overall changes were less dramatic than for LH and FAS. The LH pulses following the bolus GnRH stimulation were indistinguishable from spontaneous LH pulses occurring in normal men whereas those stimulated by the 1-, 5-, and 30-min infusions of GnRH became progressively blunted with the lowest levels of secretion occurring after the longest infusion. In sharp contrast, FAS pulse parameters in the GnRH-deficient subjects greatly exceeded those of normal men regardless of the contour of the GnRH stimulus, whereas mean FSH levels were all modestly (although significantly) higher than those of normal adult men. These results demonstrate that the pituitary is sensitive to subtle changes in the contour of the GnRH stimulus, with a more prolonged duration of GnRH stimulation resulting in a diminished pituitary response. Alterations of the contour of endogenous GnRH secretion may represent an additional mechanism for altering gonadotrope function and provide additional evidence for the differential regulation of LH, FAS, and FSH by GnRH. However, the previously reported elevated levels of FAS secretion in GnRH-deficient men undergoing long-term GnRH replacement are not explained by abnormalities of GnRH contour.

Aerosol transport and deposition in the rhythmically expanding pulmonary acinus.

Abstract: Little is known about factors controlling the dynamics of aerosol dispersion and deposition in the lung periphery, though this knowledge becomes increasingly important in many fields such as environmental and occupational exposure, diagnostic applications, and therapeutic deliver of drugs via aerosols. For the last several years, we have been studying aerosol behavior in the pulmonary acinus, where the airway structure and the associated fluid mechanics are distinctly different from those in the conducting airways. Our major research efforts have been focused on the basic physics underlying acinar fluid mechanics and particle dynamics, which are likely to be conditioned by the two key geometric factors of acinar airways: structural alveolation and rhythmic expansion and contraction of the alveolar walls. A combination of computational and experimental analyses revealed that due to these unique geometric features acinar flow can be extremely complex despite the low Reynolds number, and can have su...

Alveolar surface area-to-lung volume ratio in oleic acid-induced pulmonary edema

Abstract: It is unknown how the in vivo alveolar surface area-to-volume ratio (S/V) changes in low-pressure pulmonary edema. Here, the S/V is the area of the air-tissue interface per unit total volume (air plus tissue). We hypothesized that in oleic acid (OA)-induced edema inactivation of the pulmonary surfactant may increase surface tension and decrease the S/V at any given lung volume. OA (0.04 mg/kg) was intravenously injected into dogs. We measured the in vivo S/V (equivalent to the inverse of optical mean free path by light-scattering stereology and the pressure-volume (PV) curve 60-90 min after OA administration. OA administration decreased the lung volume at each transpulmonary pressure and increased the wet-to-dry weight ratio. The S/V decreased after OA administration (optical mean free path increased). The air-filled PV curves shifted downward after OA, but the saline-filled PV curves after OA administration did not differ significantly from control saline-filled curves. The difference in transpulmonary pressure between air- and saline-filled PV curves (an index of the magnitude of surface tension) was increased in OA-induced pulmonary edema. This study suggests that in OA-induced pulmonary edema the alveolar surface tension increases and the S/V decreases, presumably due to inactivation of surfactant by serum leakage to alveoli.

Effect of macroscopic deformation on lung microstructure

Abstract: Butler, James P., Hiroshi Miki, Stephanie Squarcia, Rick A. Rogers, and John L. Lehr. Effect of macroscopic deformation on lung microstructure. J. Appl. Physiol.81(4): 1792–1799, 1996.—Using an ani...

Flow-induced Mixing at Low Reynolds Number in an Expanding and Contracting Alveolus Model

Abstract: A recent prospective cohort study (Dockery, 1993) has shown that particulate pollutants below a few micrometers pose the greatest health hazard. Aerosols of this size range penetrate deep into the distal region of the lung and are likely to deposit in the lung periphery. The mechanisms involved in mixing and deposition of these particles in the alveolar region, however, are still not fully understood. In prior studies it has been assumed that convective (flow-induced) mixing between inhaled particles and acinar residual gas is insignificant since the nature of acinar flow is fully viscous and reversible (Davis, 1972, Ultman, 1978). Reversibility implies that the expired gas retraces the motion of inspired gas. However, experimental data contradict this widely-accepted assertion (e.g. Heyder, et al., 1988, Anderson, et al., 1989). In studies on single breath bolus dispersion in human lung, for example, Heyder, et al., (1988) showed appreciable bolus dispersion in the lung periphery which could not be accounted for solely by the particles’ intrinsic motion (Brownian motion and gravitational sedimentation). This suggested the existence of convective mixing at the level of acinus. Although several mechanisms (Cinkotai, 1974, Yu, et al., 1977, Taulbee, et al., 1978, Otani et al., 1990, 1991, Rosental, 1992, Miki, et al., 1993) have been postulated to resolve this question, none of these mechanisms has been tested fully.